C22orf31 (chromosome 22, open reading frame 31) is a protein which in humans is encoded by the C22orf31 gene. The C22orf31 mRNA transcript has an upstream in-frame stop codon, while the protein has a domain of unknown function (DUF4662) spanning the majority of the protein-coding region. The protein has orthologs with high percent similarity in mammals. The most distant orthologs are found in species of bony fish, but C22orf31 is not found in any species of birds or amphibians.
Similar to many proteins, C22orf31 is found to be highly expressed in the testes. Analysis of in vivo mature oocytes has revealed increased levels of C22orf31 while promoter analysis has identified transcription factors for C22orf31 that are active during myeloid cell differentiation.
Gene C22orf31 is located on the minus strand of chromosome 22 at 20q12.1. The gene is 3,172 base pairs long and spans from chr22: 29,058,672 to 29,061,844. C22orf31 contains 3 exons and is also known by the aliases BK747E2.1 and HS747E2A.
Transcript There is one transcript of C22orf31. The mRNA sequence is 1,070 base pairs long and contains an upstream in-frame stop codon from nucleotide 122–124.
Protein
General properties The protein encoded by C22orf31 is 290 amino acids in length with a predicted molecular mass of 33kDa. The isoelectric point of the protein is 10, indicating that the pH of the protein is basic. The C22orf31 protein contains a domain of unknown function (DUF4662) from amino acid 2 – 263. The secondary and tertiary structure of this protein is not well known.
Isoforms C22orf31 has two protein isoforms. A comparison of these isoforms is shown in the table below. +C22orf31 IsoformsProteinAccession #Size (AA) FeaturesC22orf31 [Homo sapiens]NP_056185290DUF4662 (AA 2-263)Uncharacterized protein C22orf31 isoform X1 [Homo sapiens]XP_016884230249DUF4662 (AA 1-221)Uncharacterized protein C22orf31 isoform X2 [Homo sapiens]XP_005261548186DUF4662 (AA 40-158)
Composition The protein derived from C22orf31 is considered somewhat rich in lysine and somewhat poor in phenylalanine compared to the composition of the average human protein. There are no positive, negative, mixed, or uncharged segments in C22orf31. There are also no transmembrane components or signal peptides in the protein.
Regulation
Gene level regulation Transcription factor binding sites The C22orf31 promoter has many transcription factor binding sites. C22orf31's transcription factors are commonly found in immortalized liver cancer cell lines (HepG2) and immortalized myelogenous leukemia cell lines (K562). The presence of C/EBP epsilon suggests a role for C22orf31 in myeloid cell differentiation. The presence of ARNT, which is typically associated with hypoxia-inducible factor 1 alpha, suggests a role for C22orf31 in the formation of acute myeloblastic leukemia.
Expression C22orf31 has been found to have moderate expression in the testes and low amounts of expression in the brain and ovaries. The protein is also expressed in fetal tissue as well as adult tissues. C22orf31 has been seen to have increased conditional expression in vivo matured oocytes in comparison to metaphase II oocytes.
Transcript level regulation There are no microRNA binding sites found in C22orf31. Three functionally important stem loops are predicted in both the 3' UTR and 5' UTR of C22orf31.
Protein Level Regulation
C22orf31 is predicted to undergo several types of post-translational modifications. With a high degree of certainty, it is predicted that C22orf31 undergoes O-glycosylation, glycation, phosphorylation, and O-GlcNAcylation. Only two phosphorylation sites are located in highly conserved regions of the protein. These modifications can be seen in the conceptual translation on the right.
Homology/evolution
Paralogs No human paralogs for C22orf31 have been identified.
Orthologs Orthologs of the C22orf31 protein exist predominantly in mammals. However, the most distant orthologs are found in bony fish, with no orthologs being identified in amphibians or birds. Some of the major taxon groups that C22orf31 orthologs belong to include: bovidae, eulipotyphyla, cetacea, diprotodontia, vertebrata, and rodentia.
A list of 20 C22orf31 orthologs can be seen below, organized first by ascending date of divergence and second by descending percent identity with human C22orf31. + C22orf31 Orthologs Genus speciesCommon NameTaxonDate of Divergence (MYA)Accession #Length (AA)% identity w/ human% similarity w/ human Homo sapiensHumanHomonidae0NP_056185.1 290100100Miniopterus natalensisNatal Long-fingered BatChiroptera94XP_016054130.1 30178.4582.1Physeter catodonSperm whaleCetacea94XP_023976708.1 30775.6878.8Bison bison bisonBisonBovidae94XP_010827019.12927579.5Mustela putorius furoDomestic ferretMustelidae94XP_012918895.1 39573.3160.4Ovis ariesSheepBovidae94XP_027836065.1 31573.272.7Suricata suricattaMeerkatCarnivora94XP_029777390.1 29672.3981.1Manis javanicaMalayan pangolinManidae94XP_017520770.1 30272.378.2Lagenorhynchus obliquidensPacific white-sided dolphinCetacea94XP_026981083.1 30771.1476Orcinus orcaKiller whaleCetacea94XP_004283847.1 27168.6272.6Globicephala melasLong-finned pilot whaleCetacea94XP_030715704.128768.2874.1Neophocaena asiaeorientalis Yangtze finless porpoiseCetacea94XP_024623713.1 32466.0470.2Sorex araneusEuropean shrewEulipotyphla94XP_004615674.1 32564.1163.1Condylura cristataStar-nosed moleRodentia94XP_004690724.1 34762.5459.2Loxodonta africanaAfrican bush elephantPaenungulates102XP_023415096.1 53678.5246.6Chrysochloris asiaticaCape golden moleRodentia102XP_006869362.1 46077.753.9Dasypus novemcinctusNine-banded armadilloXenarthrans102XP_023445504.1 30575.4479Echinops telfairiSmall Madagascar hedgehogEulipotyphla102XP_012863338.2 30068.0173.4Phascolarctos cinereusKoalaDiprotodontia160XP_020852397.1 30249.1960.8Vombatus ursinusCommon wombatDiprotodontia160XP_027718888.1 37848.8748.8Myripristis murdjanPinecone soldierfishVertebrata433XP_029922652.118448.9827Cottoperca gobioCottoperca Vertebrata433XP_029301846.117134.0422.4Astyanax mexicanusMexican tetraVertebrata433XP_022533372.120826.3626.3
Divergence
When compared to other proteins, namely fibrinogen alpha chain and cytochrome c, C22orf31 is a moderately evolving protein. This was determined by calculating the corrected percent divergence, using molecular clock equations, of different orthologs for each protein in comparison to their date of divergence. A physical representation of this information can be seen in the divergence graph on the right.
Interacting Proteins C22orf31 interacts physically with 3 different proteins, according to the BioGRID, Mentha, and IntAct protein interaction browsers. In particular, C22orf31 interacts with two histone deacetylases (HDAC1 and HDAC2) and the protein Lacritin (LACRT). These interactions were determined using high-throughput affinity-purification mass spectrometry A biochemical association has also been determined through protein microarray between C22orf31 and F-box protein 7 (FBOX7). All of these proteins, with additional information, are shown in the table below. + C22orf31 Interacting ProteinsProtein Name AbbreviationInteraction Type Score Interaction Detection Method Histone deacetylase 1HDAC1Physical association 0.9017 Affinity chromatographyHistone deacetylase 2HDAC2Physical association0.9213 Affinity chromatographyLacritinLACRTPhysical association0.9886 Affinity chromatographyF-box protein 7FBOX7Biochemical association -Protein microarray The score for each protein in the table refers to the level of confidence of the prediction protein interaction with C22orf31 on a scale from 0–1, 1 being more confident.
Clinical significance
Pathology Increased in vivo expression of C22orf31 in mature oocytes suggests that the gene plays a role in oocyte development.
Disease The predicted transcription factor binding sites of C22orf31 could possibly suggest a role for the gene in myeloid cell differentiation and the formation of acute myeloblastic leukemia.
References